This proposal is a resubmission of "Intentional weight reduction and physical and cognitive function". Obesity is associated with physical disability through both direct pathways (e.g., lower extremity pain, insufficient muscle strength) and indirect pathways (obesity-related comorbidities and inflammation). Furthermore, diabetes, a major obesity-related health condition, is associated with increased risk of disability and accelerated declines in physical and cognitive function. Our preliminary data suggest that intentional weight loss improves physical function, and there is strong circumstantial evidence that it would also benefit cognitive function. To evaluate the role of intentional weight loss on physical and cognitive function, we propose an ancillary study to the on-going Look AHEAD (Action for Health in Diabetes) trial. Look AHEAD is a multi-center, randomized clinical trial to examine the effects of a 4-year lifestyle intervention designed to achieve and maintain weight loss through decreased caloric intake and exercise in overweight or obese men and women aged 45-74 years with type 2 diabetes. We propose to add validated and well-established measures of physical and cognitive performance to the year 8 follow-up visit - during the trial's weight maintenance phase - in 1002 participants at 4 of the 16 Look AHEAD field sites (Colorado, Memphis, Pennington and Pittsburgh). The specific aims of this ancillary study are: 1) To determine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on physical function;and 2) To determine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on cognitive function. In addition, we hypothesize that in the intervention group, larger initial weight loss, better weight loss maintenance, and higher physical activity will be associated with better physical and cognitive function. We also hypothesize that in the control group weight loss will be associated with worse physical and cognitive function than in those who are weight stable or who have gained weight. The number of obese older adults is rising rapidly and there are few data to guide an evidence-based clinical response to their management. The results of this study will provide the first direct evidence of the role of long-term intentional weight loss on the maintenance of physical and cognitive function in older obese adults with diabetes. Since this study is being done as an ancillary study to an on-going trial it can be done in a timely and cost-efficient manner. PUBLIC HEALTH RELEVANCE: Given the high prevalence of obesity and diabetes in older adults, there is a clear public health imperative to better understand the functional implications of intentional weight loss. This proposal, taking advantage of an existing intervention study, the Look AHEAD trial, will advance our understanding in an efficient and cost- effective manner.